Effect of the selective mitochondrial KATP channel opener nicorandil on the QT prolongation and myocardial damage induced by amitriptyline in rats
Journal of Pharmacy and Pharmacology, cilt.75, sa.3, ss.415-426, 2023 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 75 Sayı: 3
- Basım Tarihi: 2023
- Doi Numarası: 10.1093/jpp/rgac089
- Dergi Adı: Journal of Pharmacy and Pharmacology
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, Food Science & Technology Abstracts, International Pharmaceutical Abstracts, Veterinary Science Database
- Sayfa Sayıları: ss.415-426
- Anahtar Kelimeler: amitriptyline, cardiotoxicity, mitoKATP channel, nicorandil, QT prolongation
- Trakya Üniversitesi Adresli: Evet
Özet
Objectives The aim of this study is to evaluate the protective effect of nicorandil, a selective mitochondrial KATP channel opener, on QT prolongation and myocardial damage induced by amitriptyline. Methods The dose of amitriptyline (intraperitoneal, i.p.) that prolong the QT interval was found 75 mg/kg. Rats were randomized into five groups the control group, amitriptyline group, nicorandil (selective mitochondrial KATP channel opener, 3 mg/kg i.p.) + amitriptyline group, 5-hdyroxydecanoate (5-HD, selective mitochondrial KATP channel blocker, 10 mg/kg i.p.) + amitriptyline group and 5-HD + nicorandil + amitriptyline group. Cardiac parameters, biochemical and histomorphological/immunohistochemical examinations were evaluated. p < 0.05 was accepted as statistically significant. Key findings Amitriptyline caused statistically significant prolongation of QRS duration, QT interval and QTc interval (p < 0.05). It also caused changes in tissue oxidant (increase in malondialdehyde)/anti-oxidant (decrease in glutathione peroxidase) parameters (p < 0.05), myocardial damage and apoptosis (p < 0.01 and p < 0.001). While nicorandil administration prevented amitriptyline-induced QRS, QT, QTc prolongation (p < 0.05), myocardial damage and apoptosis (p < 0.05), it did not affect the changes in oxidative parameters (p > 0.05). Conclusions Our results suggest that nicorandil, a selective mitochondrial KATP channel opener, plays a protective role in amitriptyline-induced QT prolongation and myocardial damage. Mitochondrial KATP channel opening and anti-apoptotic effects may play a role in the cardioprotective effect of nicorandil.